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Research Line I: Oncology

The problem of cancer continues to grow at national and global level. In recent years, the understanding of the disease has greatly improved and significant technological advances have been made. However cancer is a disease of great complexity of which we still have much to learn. This creates important opportunities for the development of new diagnostic tools, treatments and prevention methods.

Background

It is now firmly established that cancer has a genetic basis. Tumors, apparently identical under microscopic observation, can have entirely different clinical courses (survival, response to treatment) that depend certainly on the alterations present in each specific patient. The success of cancer drugs that were designed to target the molecular alterations underlying tumorigenesis has proven that molecular alterations are legitimate targets for early diagnosis, prognosis and therapy.

Cancer is a dynamic entity in its own genetic foundations. The growth of a tumor from a single genetically altered cell is a gradual process of evolution that we represent in this figurative “Cancer Time Line”.

Initiation/Transformation involves one or more stable cellular changes arising spontaneously or induced by exposure to a carcinogen. This is considered to be the first step in carcinogenesis, where the cellular genome undergoes mutations, creating the potential for neoplastic development. The initiated cell can remain harmless, until an event occurs that drives cells to proliferate (Promotion), upsetting the cells balance. The neoplastic transformation can depend on several steps and require lasting and repeated exposure to the promoting stimulus.Progression is the process through which successive molecular changes in the neoplasm give rise to increasingly malignant sub-populations. The process may be divided in: an Early Phase in which the cancerous growth or tumor is still confined to the site from which it started; a Middle Phase characterized by increased growth speed and invasiveness of the tumor cells; and a Late Phase where the cells lose their adherence property, detach from the tumor mass and invade the surrounding tissues. The detached cells also enter the circulating blood and lymph and are transported to other organs/tissues away from the site of the primary growth and develop into secondary tumors at the new sites (Metastasis), until the organism succumbs.

Understanding this evolution allows us to develop not only new therapies and new molecular targets but also to optimize the therapeutic treatments already in place. We support also the concept that, like in an orchestra playing, all the cells and molecules comprising a tumor interact and engage in highly regulated reciprocal dialogues favoring malignancy. Recent studies have highlighted the extensive heterogeneity inter and intra tumor. The genome/transcriptome/proteome of the tumor micro-environment, divided in its components, is essential for understanding the progression from the initial phases to the metastatic disease.

Scientific strategy

To speed up progress in cancer research our scientific strategy focused on what is the natural evolution of cancer. Based on the cancer time line, we have developed projects that investigate, when possible, the different phases of cancer progression with different research challenges:

Prevention and early diagnosis: we know how important preventive interventions are. We must use this approach to identify and assess the factors that help to decrease the risk of contracting cancer in the first place. Early detection of cancer offers the greatest potential to improve patient survival. For many cancers, symptoms are not specific until a late stage, therefore, it is essential to find the presence of cancer in asymptomatic subjects. The possibility of survival for patients with almost all types of cancer, are significantly increased if the tumor can be diagnosed and treated at an early stage.

Better diagnosis and prognosis: Our cutting-edge research is based on the use of sophisticated technology to identify and isolate genetic and protein biomarkers that correlate with cancer. It is also necessary to identify molecular factors that are of help for a differential diagnosis more accurate and informative from a prognostic point of view.

New therapies and treatment tailoring: to find new treatments it is needed to have new perspectives and to get to know new basic molecular mechanisms. Understanding the genetic and protein aberrations underlying tumor progression and how the tumor develops resistance to treatment is the basis for the development of therapeutic strategies. Moreover, it is necessary to understand why some patients do not respond to treatment. New technologies such as gene sequencing and molecular imaging tell us that every patient has a unique type of cancer almost like one’s fingerprints, and this creates opportunities to develop more accurate and personalized treatments. Recent studies have highlighted the extensive heterogeneity 'inter and intra tumor. With time the tumor evolves due to both a natural progression and the therapeutic treatment itself. A contained and customized surgery and radiotherapy, combined with agents with precise molecular targets (genes or proteins), can dramatically improve the ability to offer a long-term survival.

One further strategic objective is to establish close collaborations with pathologists, oncologists and surgeons so that our investigations can be performed on clinical samples obtained from cancer patients and human healthy volunteers. The results obtained are then validated and functionally characterized using in vitro (cell and organ cultures) and in vivo methods. The in vivo experiments are conducted in collaboration with other institutions.

We are focusing our attention on breast cancer and brain tumors (glioblastoma). Both pathologies of great social impact, with often fatal results, the aetiology and pathogenesis of which are largely unknown.